U.S. patent application number 11/597983 was filed with the patent office on 2008-01-24 for method of detecting an analyte using a holographic sensor.
Invention is credited to Satyamoorthy Kabilan, Mei-Ching Lee, Christopher Robin Lowe.
Application Number | 20080020478 11/597983 |
Document ID | / |
Family ID | 32696777 |
Filed Date | 2008-01-24 |
United States Patent
Application |
20080020478 |
Kind Code |
A1 |
Lowe; Christopher Robin ; et
al. |
January 24, 2008 |
Method of Detecting an Analyte Using a Holographic Sensor
Abstract
A method for the detection of an analyte in a fluid, which
comprises contacting the fluid with a holographic element
comprising a medium and a hologram disposed throughout the volume
of the medium, wherein an optical characteristic of the element
changes as a result of a variation of a physical property occurring
throughout the volume of the medium, and wherein the variation
arises as a result of interaction between the medium and the
analyte; and detecting any change of the optical characteristic of
the element; wherein (a) the medium comprises a group which is
capable of reacting with the analyte, wherein the analyte or the
group is capable of existing in a plurality of forms, and the
detecting is conducted in the presence of a first catalyst which is
capable of catalysing the conversion of a relatively less reactive
form of the analyte or group to a relatively more reactive form; or
(b) the fluid comprises a component, other than the analyte, which
is capable of interacting with the medium, and the detecting is
conducted in the presence of a second catalyst capable of
catalysing the removal of said component.
Inventors: |
Lowe; Christopher Robin;
(Cambridge, GB) ; Kabilan; Satyamoorthy;
(Cambridge, GB) ; Lee; Mei-Ching; (London,
GB) |
Correspondence
Address: |
SALIWANCHIK LLOYD & SALIWANCHIK;A PROFESSIONAL ASSOCIATION
PO BOX 142950
GAINESVILLE
FL
32614-2950
US
|
Family ID: |
32696777 |
Appl. No.: |
11/597983 |
Filed: |
June 6, 2005 |
PCT Filed: |
June 6, 2005 |
PCT NO: |
PCT/GB05/02222 |
371 Date: |
August 10, 2007 |
Current U.S.
Class: |
436/127 ;
351/219; 359/2; 422/82.05; 436/164 |
Current CPC
Class: |
G01N 21/75 20130101;
G03H 1/0005 20130101; G03H 2210/55 20130101; Y10T 436/20 20150115;
G03H 1/0248 20130101; G03H 2001/0033 20130101; G01N 21/4788
20130101; G03H 1/0011 20130101; G03H 2270/55 20130101 |
Class at
Publication: |
436/127 ;
351/219; 359/002; 422/082.05; 436/164 |
International
Class: |
G01N 33/66 20060101
G01N033/66; A61B 3/10 20060101 A61B003/10; G01N 21/00 20060101
G01N021/00; G02B 5/32 20060101 G02B005/32; G01N 21/01 20060101
G01N021/01 |
Foreign Application Data
Date |
Code |
Application Number |
Jun 7, 2004 |
GB |
0412654.6 |
Claims
1. A method for the detection of an analyte in a fluid, which
comprises contacting the fluid with a holographic element
comprising a medium and a hologram disposed throughout the volume
of the medium, wherein an optical characteristic of the element
changes as a result of a variation of a physical property occurring
throughout the volume of the medium, and wherein the variation
arises as a result of interaction between the medium and the
analyte; and detecting any change of the optical characteristic of
the element; wherein (a) the medium comprises a group which is
capable of reacting with the analyte, wherein the analyte or the
group is capable of existing in a plurality of forms, and the
detecting is conducted in the presence of a first catalyst which is
capable of catalysing the conversion of a relatively less reactive
form of the analyte or group to a relatively more reactive form; or
(b) the fluid comprises a component, other than the analyte, which
is capable of interacting with the medium, and the detecting is
conducted in the presence of a second catalyst capable of
catalysing the removal of said component.
2. The method according to claim 1, wherein the analyte is
glucose.
3. The method according to claim 2, wherein condition (a) applies,
the first catalyst is mutarotase or glucose isomerase, and the
group is a phenylboronic acid group or a derivative thereof.
4. The method according to claim 2, wherein condition (b) applies,
said component is lactate and the second catalyst is lactate
oxidase or lactate dehydrogenase.
5. The method according to claim 4, wherein the second catalyst is
lactate oxidase and detection takes place in the presence of
catalase.
6. The method according to claim 1, wherein the analyte is
lactate.
7. The method according to claim 6, wherein condition (b) applies,
said component is glucose and the second catalyst is glucose
oxidase.
8. The method according to claim 1, wherein the contacting
comprises passing the fluid continuously over the element.
9. The method according to claim 1, wherein the hologram is
generated by the diffraction of light.
10. The method according to claim 1, wherein the hologram is only
visible under magnification.
11. The method according to claim 1, wherein the holographic image
is of an object or is a 2- or 3-dimensional effect.
12. The method according to claim 1, wherein the holographic
element further comprising means for producing an interference
effect when illuminated with laser light.
13. The method according to claim 12, wherein the means comprises a
depolarising layer.
14. The method according to claim 1, wherein the hologram is
viewable under white light, UV light or infra-red radiation.
15. The method according to claim 1, wherein the hologram is
viewable under specific temperature, magnetism or pressure
conditions.
16. An ophthalmic device which is suitable for use in a method for
the detection of an analyte in a fluid, and wherein said method
comprises contacting the fluid with a holographic element
comprising a medium and a hologram disposed throughout the volume
of the medium, wherein an optical characteristic of the element
changes as a result of a variation of a physical property occurring
throughout the volume of the medium, and wherein the variation
arises as a result of interaction between the medium and the
analyte, and detecting any change of the optical characteristic of
the element; wherein (a) the medium comprises a group which is
capable of reacting with the analyte, wherein the analyte or the
group is capable of existing in a plurality of forms, and the
detecting is conducted in the presence of a first catalyst which is
capable of catalysing the conversion of a relatively less reactive
form of the analyte or group to a relatively more reactive form; or
(b) the fluid comprises a component, other than the analyte which
is capable of interacting with the medium and the detecting is
conducted in the presence of a second catalyst capable of
catalysing the removal of said component; and wherein said
ophthalmic device comprises a holographic element and a first or
second catalyst.
17. The device according to claim 9, which is a contact lens.
18. The device according to claim 10, wherein the lens outer
comprises the catalyst.
19. An article suitable for use in a method for the detection of an
analyte in a fluid, wherein said method comprises contacting the
fluid with a holographic element comprising a medium and a hologram
disposed throughout the volume of the medium, wherein an optical
characteristic of the element changes as a result of a variation of
a physical property occurring throughout the volume of the medium,
and wherein the variation arises as a result of interaction between
the medium and the analyte; and detecting any change of the optical
characteristic of the element; wherein (a) the medium comprises a
group which is capable of reacting with the analyte, wherein the
analyte or the group is capable of existing in a plurality of
forms, and the detecting is conducted in the presence of a first
catalyst which is capable of catalysing the conversion of a
relatively less reactive form of the analyte or group to a
relatively more reactive form; or (b) the fluid comprises a
component, other than the analyte, which is capable of interacting
with the medium, and the detecting is conducted in the presence of
a second catalyst capable of catalysing the removal of said
component; and wherein said article comprises, a holographic
element.
20. The article according to claim 19, which is a transaction card,
banknote, passport, identification card, smart card, driving
license, share certificate, bond, cheque, cheque card, tax
banderole, gift voucher, postage stamp, rail or air ticket,
telephone card, lottery card, event ticket, credit or debit card,
business card, or an item used in consumer, brand or product
protection for the purpose of distinguishing genuine products from
counterfeit products or identifying stolen products.
21. The article according to claim 19, which is an item of
intelligent packaging.
22. The article according to claim 19, which is an industrial or
handicraft item comprising a decorative element, selected from
items of jewellery, items of clothing, fabric, furniture, toys,
gifts, household items, architecture, art, stationery and sporting
goods.
23. The article according to claim 19, which is a product or device
for use in agricultural studies, environmental studies, human or
veterinary prognostics, theranostics, diagnostics, therapy or
chemical analysis.
24. The article according to claim 23, which is a test strip, chip,
cartridge, swab, tube, pipette, contact lens, sub-conjuctival
implant, sub-dermal implant, breathalyser, catheter or a fluid
sampling or analysis device.
25. A transferable holographic film for use in a method for the
detection of an analyte in a fluid, wherein said method comprises
contacting the fluid with a holographic element comprising a medium
and a hologram disposed throughout the volume of the medium,
wherein an optical characteristic of the element changes as a
result of a variation of a physical property occurring throughout
the volume of the medium, and wherein the variation arises as a
result of interaction between the medium and the analyte; and
detecting any change of the optical characteristic of the element;
wherein (a) the medium comprises a group which is capable of
reacting with the analyte, wherein the analyte or the group is
capable of existing in a plurality of forms, and the detecting is
conducted in the presence of a first catalyst which is capable of
catalysing the conversion of a relatively less reactive form of the
analyte or group to a relatively more reactive form; or (b) the
fluid comprises a component, other than the analyte, which is
capable of interacting with the medium, and the detecting is
conducted in the presence of a second catalyst capable of
catalysing the removal of said component; and wherein said film
comprises a holographic element and a first or second catalyst.
26. The film according to claim 25, which is present on a hot
stamping tape.
27. A method of enhancing the security of an article, wherein said
method comprises transferring onto the article the holographic
element from a transferable holographic film wherein said film is
suitable for use in a method for the detection of an analyte in a
fluid, wherein said method for detection comprises contacting the
fluid with a holographic element comprising a medium and a hologram
disposed throughout the volume of the medium, wherein an optical
characteristic of the element changes as a result of a variation of
a physical property occurring throughout the volume of the medium,
and wherein the variation arises as a result of interaction between
the medium and the analyte; and detecting any change of the optical
characteristic of the element; wherein (a) the medium comprises a
group which is capable of reacting with the analyte, wherein the
analyte or the group is capable of existing in a plurality of
forms, and the detecting is conducted in the presence of a first
catalyst which is capable of catalysing the conversion of a
relatively less reactive form of the analyte or group to a
relatively more reactive form; or (b) the fluid comprises a
component, other than the analyte, which is capable of interacting
with the medium, and the detecting is conducted in the presence of
a second catalyst capable of catalysing the removal of said
component; and wherein said film comprises a holographic element
and a first or second catalyst.
28. A product suitable for use in a method for the detection of an
analyte in a fluid, wherein said method comprises contacting the
fluid with a holographic element comprising a medium and a hologram
disposed throughout the volume of the medium, wherein an optical
characteristic of the element changes as a result of a variation of
a physical property occurring throughout the volume of the medium,
and wherein the variation arises as a result of interaction between
the medium and the analyte, and detecting any change of the optical
characteristic of the element; wherein (a) the medium comprises a
group which is capable of reacting with the analyte, wherein the
analyte or the group is capable of existing in a plurality of
forms, and the detecting is conducted in the presence of a first
catalyst which is capable of catalysing the conversion of a
relatively less reactive form of the analyte or group to a
relatively more reactive form; or (b) the fluid comprises a
component, other than the analyte which is capable of interacting
with the medium, and the detecting is conducted in the presence of
a second catalyst capable of catalysing the removal of said
component; and wherein said product comprises a holographic element
that is capable of generating data from said element.
29. A system which uses data generated by a product for data
storage, control, transmission, reporting and/or modeling wherein
said product is suitable for use in the detection of an analyte in
a fluid, which comprises contacting the fluid with a holographic
element comprising a medium and a hologram disposed throughout the
volume of the medium, wherein an optical characteristic of the
element changes as a result of a variation of a physical property
occurring throughout the volume of the medium, and wherein the
variation arises as a result of interaction between the medium and
the analyte; and detecting any change of the optical characteristic
of the element; wherein (a) the medium comprises a group which is
capable of reacting with the analyte, wherein the analyte or the
group is capable of existing in a plurality of forms, and the
detecting is conducted in the presence of a first catalyst which is
capable of catalysing the conversion of a relatively less reactive
form of the analyte or group to a relatively more reactive form; or
(b) the fluid comprises a component, other than the analyte, which
is capable of interacting with the medium, and the detecting is
conducted in the presence of a second catalyst capable of
catalysing the removal of said component; and wherein said product
comprises a holographic element that is capable of generating data
from said element.
Description
FIELD OF THE INVENTION
[0001] This invention relates to a method for the detection of an
analyte using a holographic sensor.
BACKGROUND TO THE INVENTION
[0002] WO9526499 discloses a holographic sensor for the detection
of an analyte. This sensor comprises a holographic element
comprising a support medium and a hologram disposed throughout the
volume of the medium. An optical characteristic of the element
changes a result of a variation of a physical property occurring
throughout the volume of the medium, the variation arising as a
result of reaction between the medium and the analyte. By
monitoring any change in the optical characteristic, the presence
of the analyte can be detected. WO03/087789 describes a process for
the continuous sensing of an analyte using a holographic
sensor.
[0003] A particular analyte of interest is glucose. There is a need
for minimally invasive, easy-to-use glucose sensors, particularly
ophthalmic glucose sensors. The concentration of glucose in the
blood is typically of the order of 20 mM, whereas in the eye it is
about 0.1 mM. The levels of glucose in the eye are known to
correlate to those in the blood. Thus, blood levels of glucose can
be monitored indirectly by measuring the levels in an ocular fluid
such as tears.
[0004] Glucose (also known as D-glucose) occurs in five different
forms. The four cyclic forms of glucose, namely
.alpha.-D-glucopyranose, .beta.-D-glucopyranose,
.alpha.-D-glucofuranose and .beta.-D-glucofuranose, coexist in
equilibrium with the acyclic form, D-glucose aldehyde, via a
process called "complex mutarotation". Typically, the proportions
of the .alpha.-D-glucopyranose, .beta.-D-glucopyranose,
.alpha.-D-glucofuranose, .beta.-D-glucofuranose and D-glucose
aldehyde are about 39.4, 60.2, 0.2, 0.2 and 0.001% respectively
(Shoji et al, J. Am. Chem. Soc., 124(42), 12486-93).
[0005] A well-documented reaction is that of glucose with boronic
acid compounds. It has been suggested that the binding of glucose
to a boronic acid, RB(OH).sub.2, occurs only when the glucose is in
the .alpha.-D-glucofuranose form (Shoji et al). Other studies
(Shiomi et al, J. Chem. Soc. Perkin Trans. 1, 2111-2117), however,
postulate that the .alpha.-D-pyranose form that may also bind,
provided the NMR coupling constants are assigned correctly.
Furthermore, it has been suggested that the boronic acid must be in
a tetrahedral (i.e. RB(OH).sub.3.sup.-), as opposed to a trigonal,
conformation. It has been suggested that boronic acids
preferentially bind to diols which are in a cis conformation (Liu
et al, J. Organomet. Chem., 493(1-2), 91-94). The reaction is fully
reversible, the pH at which the conformational change occurs
strongly influenced by the structure of R. R is preferably a phenyl
group or derivative thereof. Generally, only a small proportion of
the .alpha.-D-glucofuranose form is present, and so little reaction
takes place, often at a low rate.
[0006] The extent of reaction between glucose and a boronic acid
can be increased by varying the extent of complex mutarotation. The
enzyme mutarotase catalyses the conversion of the .beta.-forms (via
the linear form) to .alpha.-D-glucofuranose. Alternatively, the
extent of reaction can be increased by first converting glucose to
fructose or ribose, using an enzyme such as glucose isomerase.
Fructose and ribose react with boronic acids in an analogous manner
to glucose.
SUMMARY OF THE INVENTION
[0007] The present invention is based upon the realisation that the
response of a holographic sensor can be increased by detecting any
interaction between the holographic support medium and analyte in
the presence of an agent, more specifically a catalyst, which
enhances that interaction. For example, a holographic sensor
comprising pendant boronic acid groups may be used for the
detection of glucose. However, since the levels of the
.alpha.-D-glucofuranose form are generally very low, the time and
level of response of such a sensor may be poor. The response may be
dramatically enhanced by carrying out detection in the presence an
enzyme such as mutarotase or glucose isomerase.
[0008] A first aspect of the invention is a method for the
detection of an analyte in a fluid, which comprises contacting the
fluid with a holographic element comprising a medium and a hologram
disposed throughout the volume of the medium, wherein an optical
characteristic of the element changes as a result of a variation of
a physical property occurring throughout the volume of the medium,
and wherein the variation arises as a result of interaction between
the medium and the analyte; and detecting any change of the optical
characteristic of the element; wherein
[0009] (a) the medium comprises a group which is capable of
reacting with the analyte, wherein the analyte or the group is
capable of existing in a plurality of forms, and the detecting is
conducted in the presence of a first catalyst which is capable of
catalysing the conversion of a relatively less reactive form of the
analyte or group to a relatively more reactive form; or
[0010] (b) the fluid comprises a component, other than the analyte,
which is capable of interacting with the medium, and the detecting
is conducted in the presence of a second catalyst capable of
catalysing the removal of said component.
[0011] In the case of glucose, detection preferably takes place in
the presence of a catalyst which catalyses the conversion of
.alpha.-D-glucopyranose, .beta.-D-glucofuranose and/or D-glucose
aldehyde to .alpha.-D-glucofuranose. More preferably, detection
takes place in the presence of mutarotase and/or glucose
isomerase.
[0012] Another aspect of the invention is an ophthalmic device
which comprises a holographic element and a catalyst as defined
above. The insert may be in the form of a contact lens or
implantable device.
DESCRIPTION OF THE INVENTION
[0013] The term "glucose" as used herein refers to the known cyclic
and linear forms of glucose.
[0014] The term "ophthalmic device" as used herein refers to
contact lenses (both hard and soft), corneal onlays, implantable
ophthalmic devices and the like.
[0015] The term "contact lens" as used herein refers to any hard or
soft lens used on the eye or ocular vicinity for vision correction,
diagnosis, sample collection, drug delivery, wound healing,
cosmetic appearance or other ophthalmic application. The lens may
be a daily-disposable, daily-wear or extended-wear lens.
[0016] The term "implantable ophthalmic device" as used herein
refers to an ophthalmic device which is used in, on or about the
eye or ocular vicinity. Such devices include intraocular lenses,
subconjunctival lenses, intracorneal lenses, and shunts/implants
(e.g. a stent or glaucoma shunt) that can rest in the cul de sac of
an eye.
[0017] The interaction between the medium and the analyte may be
physical and/or chemical. The sensor may allow for the continuous
detection of an analyte.
[0018] The analyte may be able to exist in a plurality of forms. In
this case, a catalyst may be used that catalyses the conversion of
the analyte to a more reactive form. An example of such an analyte
is glucose, which. via mutarotation is able to exist in five
different forms. Thus, in the case of glucose, the catalyst may be
an enzyme such as mutarotase or glucose isomerase, allowing the
rate of conversion to .alpha.-D-glucofuranose to increase. When a
medium comprising phenylboronic acid or like groups is used, the
extent of reaction between glucose and the medium will be
enhanced.
[0019] Lactate (lactic acid) is known to interfere with the sensing
of glucose. This is a particular problem in the eye, where lactate
is present at relatively high concentration. The catalyst thus may
promote the removal of lactate. For example, lactate oxidase may be
used. This enzyme catalyses the breakdown of lactate to (via a
pyruvate intermediate) hydrogen peroxide. Hydrogen peroxide may
react with silver and thus, if the sensor is silver-based, it is
preferred that an enzyme such as catalase is present to remove any
unwanted hydrogen peroxide produced. An alternative to lactate
oxidase is lactate dehydrogenase, which converts lactic acid into
pyruvate without the production of hydrogen peroxide.
[0020] Conversely, should lactate be the analyte of interest then
it may be desirable to remove glucose from the system. In this
case, an enzyme such as glucose oxidase may be used.
[0021] The interaction between the medium and analyte can be
detected remotely, using non-ionising radiation. The extent of
interaction is reflected in the degree of change of the physical
property, which is detected as a variation in an optical
characteristic, preferably a shift in wavelength of non-ionising
radiation.
[0022] The property of the holographic element which varies may be
its charge density, volume, shape, density, viscosity, strength,
hardness, charge, hydrophobicity, swellability, integrity,
cross-link density or any other physical property. Variation of the
or each physical property, in turn, causes a variation of an
optical characteristic, such as polarisability, reflectance,
refractance or absorbance of the holographic element.
[0023] The hologram may be disposed on or in, part of or throughout
the bulk of the volume of the support medium. An illuminating
source of non-ionising radiation, for example visible light, may be
used to observe variation(s) in the, or each, optical
characteristic of the holographic element.
[0024] The holographic effect may be exhibited by illumination
(e.g. under white light, UV or infra-red radiation), specific
temperature, magnetic or pressure conditions, or particular
chemical, biochemical or biological stimuli. The hologram may be an
image of an object or a 2- or 3-dimensional effect, and may be in
the form of a pattern which is only visible under
magnification.
[0025] The hologram can be generated by the diffraction of light.
The holographic element may further comprise means for producing an
interference effect when illuminated with laser light and such
means can comprises a depolarising layer.
[0026] More than one hologram may be supported on, or in, a
holographic element. Means may be provided to detect the or each
variation in radiation emanating from the or each hologram, arising
as a result of a variation in the or each optical characteristic.
The holographic elements may be dimensioned and arranged so as to
sense two or more independent events/species and to affect,
simultaneously, or otherwise, radiation in two or more different
ways. Holographic elements may be provided in the form of an
array.
[0027] The holographic support medium may be obtained by the
polymerisation of monomers, such as (meth)acrylamide and/or
(meth)acrylate-derived comonomers. In particular, the monomer HEMA
(hydroxyethyl methacrylate) is readily polymerisable and
cross-linkable. PolyHEMA is a versatile support material since it
is swellable, hydrophilic and widely biocompatible.
[0028] Other examples of holographic support media which may be
modified to include boronic acid groups are gelatin, K-carageenan,
agar, agarose, polyvinyl alcohol (PVA), sol-gels (as broadly
classified), hydro-gels (as broadly classified), and acrylates.
[0029] A parameter determining the response of a holographic
element is the extent of cross-linking. The number of cross-linking
points due to polymerisation of monomers should not be so great
that complex formation between polymer and analyte-binding groups
is relatively low, since the polymer film may become too rigid.
This may inhibit the swelling of the support medium.
[0030] In a preferred embodiment, an insert of the invention is in
the form of a contact lens. The lens may be manufactured using any
suitable material known in the art. The lens material may be formed
by the polymerisation of one or more monomers and optionally one or
more prepolymers. The material may comprise a photoinitiator,
visibility tinting agent, UV-blocking agent and/or a
photosensitiser.
[0031] A preferred group of lens materials is prepolymers which are
water-soluble and/or meltable. It is preferred that the material
comprises one or more prepolymers which are in a substantially pure
form (e.g. purified by ultrafiltration). Preferred prepolymers
include water-soluble crosslinkable poly(vinyl alcohol) prepolymers
(as described in U.S. Pat. No. 5,583,163 and U.S. Pat. No.
6,303,687); a water-soluble vinyl group-terminated polyurethane,
obtainable by reacting an isocyanate-capped polyurethane with an
ethylenically unsaturated amine (primary or secondary amine) or an
ethylenically unsaturated monohydroxy compound, wherein the
isocyanate-capped polyurethane can be a copolymerisation product of
at least one polyalkylene glycol, a compound containing at least 2
hydroxyl groups, and at least one compound with two or more
isocyanate groups; derivatives of a polyvinyl alcohol,
polyethyleneimine or polyvinylamine (see, for example, U.S. Pat.
No. 5,849,841); a water-soluble cross-linkable polyurea prepolymer
as described in U.S. Pat. No. 6,479,587; cross-linkable
polyacrylamide; cross-linkable statistical copolymers of vinyl
lactam, MMA and a comonomer, as disclosed in EP0655470 and U.S.
Pat. No. 5,712,356; cross-linkable copolymers of vinyl lactam,
vinyl acetate and vinyl alcohol, as disclosed in EP0712867 and U.S.
Pat. No. 5,665,840; polyether-polyester copolymers with
cross-linkable side chains, as disclosed in EP0932635; branched
polyalkylene glycol-urethane prepolymers, as disclosed in EP0958315
and U.S. Pat. No. 6,165,408; polyalkylene
glycol-tetra(meth)acrylate prepolymers, as disclosed in EP0961941
and U.S. Pat. No. 6,221,303; and cross-linkable polyallylamine
gluconolactone prepolymers, as disclosed in WO00/31150.
[0032] The lens may comprise a hydrogel material. Typically,
hydrogel materials are polymeric materials which are capable of
absorbing at least 10% by weight of water when fully hydrated.
Hydrogel materials include polyvinyl alcohol (PVA), modified PVA
(e.g. nelfilcon A), poly(hydroxyethyl methacrylate), poly(vinyl
pyrrolidone), PVA with a poly(carboxylic acid) (e.g. carbopol),
poly(ethylene glycol), polyacrylamide, polymethacrylamide,
silicone-containing hydrogels, polyurethane, polyurea, and the
like.
[0033] Alternatively, the ophthalmic device may be an implantable
ophthalmic device. Glucose levels in tears may be much lower than
blood glucose levels. With an implantable ophthalmic sensor, one
can monitor glucose levels in aqueous humor or interstitial fluid,
where glucose levels can be much higher than glucose levels in
tears. Preferably, the device is in the form of a subconjunctive
implant, intracorneal lens, stent or glaucoma shunt.
[0034] Particularly when the analyte is glucose or lactate, it is
preferred that the lens outer comprises a catalyst of the
invention. In this way, it may be possible to block the
interference of a component other than the analyte, which interacts
with the medium.
[0035] The method of the invention may be used to authenticate an
article. Where the holographic element is a sensor, the sensor may
be applied to an article using a transferable holographic film
which is, for example, provided on a hot stamping tape. The article
may be a transaction card, banknote, passport, identification card,
smart card, driving licence, share certificate, bond, cheque,
cheque card, tax banderole, gift voucher, postage stamp, rail or
air ticket, telephone card, lottery card, event ticket, credit or
debit card, business card, or an item used in consumer, brand and
product protection for the purpose of distinguishing genuine
products from counterfeit products and identifying stolen products.
The sensors may be used to provide product and pack information for
intelligent packaging applications. "Intelligent packaging" refers
to a system that comprises part of, or an attachment to, a
container, wrapper or enclosure, to monitor, indicate or test
product information or quality or environmental conditions that
will affect product quality, shelf life or safety and typical
applications, such as indicators showing time-temperature,
freshness, moisture, alcohol, gas, physical damage and the
like.
[0036] Alternatively, the sensors can be applied to products with a
decorative element or application such as any industrial or
handicraft item including but not limited to items of jewellery,
items of clothing (including footwear), fabric, furniture, toys,
gifts, household items (including crockery and glassware),
architecture (including glass, tile, paint, metals, bricks,
ceramics, wood, plastics and other internal and external
installations), art (including pictures, sculpture, pottery and
light installations), stationery (including greetings cards,
letterheads and promotional material) and sporting goods.
[0037] The invention is particularly relevant to a diagnostic
device such as a test strip, chip, cartridge, swab, tube, pipette
or any form of liquid sampling or testing device, and products or
processes relating to human or veterinary prognostics,
theranostics, diagnostics or medicines. The sensors may be used in
a contact lens, sub-conjuctival implant, sub-dermal implant, test
strip, chip, cartridge, swab, tube, breathalyser, catheter, any
form or blood, urine or body fluid sampling or analysis device. The
sensors may also be used in a product or process relating to
petrochemical and chemical analysis and testing, for example in a
testing device such as a test strip, chip, cartridge, swab, tube,
pipette or any form of liquid sampling or analysis device.
[0038] The present invention also extends to a product suitable for
use in the method of the invention comprising a holographic element
where the product is capable of generating data from the
holographic element and to a system which uses the data for data
storage, control, transmission, reporting and/or modelling.
[0039] The following Examples illustrate the invention, the
exception being Example 1, which illustrates features of the
invention.
[0040] In the Examples, a holographic sensor comprising a polymeric
support medium containing 12 mol % 3-acrylamidophenylboronic acid
(the synthesis of which is described in WO2004/081624). The
.alpha.- and .beta.-D-glucopyranose forms of glucose were obtained
from Sigma in solid form. Mutarotase was purchased from Biozyme and
originated from porcine kidney. Glucose isomerase was obtained from
Hampton Research and originated from Streptomyces rubiginosus.
Lactate oxidase was purchased from Sigma and originated from
Pediococcus sp. Detection took place in PBS, pH 7.4 at 30.degree.
C.
EXAMPLE 1
[0041] Freshly-dissolved .alpha.-glucopyranose was detected using a
holographic sensor and the rate of binding recorded. Also, a
solution of .alpha.-glucopyranose was left overnight to
equilibrate, and the rate of binding then determined. The
experiment was repeated using .beta.-glucopyranose. The rate of
reaction was calculated by determining the time taken for the
holographic sensor to reach 50% of its final equilibrium peak
diffraction wavelength (i.e. the half/life) using 2 mM of the
solutions.
[0042] Results are shown in FIG. 1. It is evident that the
freshly-dissolved .alpha.-glucopyranose form binds to the pendant
phenylboronic acid group at a faster rate than freshly-dissolved
.beta.-glucopyranose. In the case of the two solutions left
overnight, the rates were almost identical. These results suggest
that the sensor binds the .alpha.-glucopyranose form more readily
than the .beta.-glucopyranose form. The similar rates observed for
the solutions left overnight suggests an equilibrium effect, i.e.
the .beta.-form is converting into the .alpha.-form. The
interconversion between the two forms is very slow and is likely to
account for the slow binding kinetics observed.
EXAMPLE 2
[0043] A 2 mM glucose solution was made up and left overnight to
equilibrate. A holographic sensor was then used to detect glucose
in the presence of varying amounts of mutarotase. The initial rate
of response, i.e. the initial increase in peak diffraction
wavelength upon addition of the glucose solution, was
determined.
[0044] The results are shown in FIG. 2 and indicate that, at
relatively lower concentrations of mutarotase, the initial rate of
binding is faster than when mutarotase is absent. The optimum
amount of mutarotase was found to be 0.25 mg/ml, which increased
the rate of reaction by 54% relative to the control.
EXAMPLE 3
[0045] The effect of glucose isomerase on the binding of glucose to
a holographic sensor was determined. Dialysis of glucose isomerase
was performed to remove the buffer that it was suspended in. The
holographic sensor allowed to equilibrate with 1 mM MgSO.sub.4,
Mg.sup.2+ being a co-factor for glucose isomerase. A 0.5 mM glucose
solution was then added to the sensor in the presence of varying
amounts of glucose isomerase.
[0046] Results are shown in FIG. 3. It can be seen that the
addition of glucose isomerase enhances the sensitivity of the
sensor. It is also noticeable that, the greater the quantity of
glucose isomerase added, the longer the system takes to
equilibrate. The initial rates of reaction are also much faster
than that of the control.
EXAMPLE 4
[0047] A holographic sensor was placed in a cuvette with PBS, and
12.5 units of lactate oxidase added. Once the system had
equilibrated, 2 mM lactate solution was added and the shift in peak
diffraction wavelength detected over time.
[0048] The results are shown in FIG. 4. Initially, the support
medium of the sensor swelled up as it bound lactate but then
contracted as lactate began to be consumed by lactate oxidase. The
peak wavelength eventually returned to its initial value,
indicating that all the lactate had been converted to pyruvate.
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